It is known that 5 alpha-reduction of the delta 4 double bond in the steroid A ring and formation of 5 alpha-dihydrotestosterone (DHT) is a critical step for androgen activation. Increased formation of DHT has been demonstrated in certain cases of carcinoma and fibroadenoma of the human breast implying a potential pathophysiologic role for androgen metabolism in these neoplasms. The importance of androgen metabolism in carcinoma of the human prostate is well documented. We recently demonstrated 5 alpha-reductase activity in human endometrium and myometrium and noted that this activity was elevated in cases of benign uterine neoplasms. From preliminary results it appears that 5 alpha-reductase activity is also elevated in human uterine malignant neoplasms. If androgens are important pathophysiologically in human uterine neoplastic disease, then it should be possible to demonstrate physiologically significant interactions between active-androgens and human uterine neoplastic tissues. It is known that human normal uteri contain a cytoplasmic receptor protein specific for DHT. The object of the proposed research is to correlate the levels of 5 alpha-reduction of testosterone in human normal uteri as well benign and malignant uterine neoplasms with: 1) the levels of cytoplasmic receptors specific for DHT; and 2) pertinent pathological findings. Agar gel electrophoresis at low temperature will be used to determine the levels of cytoplasmic DHT receptors and the ability of antiandrogens to compete with DHT for binding to these receptors. This study will clarify the role of androgens in the human uterus, both normal and neoplastic, and thus could yield useful therapeutic information.